The present invention relates to the art of processing material, and to a method of harnessing natural mass formation forces and the products resulting therefrom. More particularly, the present invention relates to a delivery system for administering a bio-affecting agent to a recipient without use of a conventional delivery format.
In the past, it has been common to deliver various medicaments and other active ingredients by conventional delivery formats such as tablets and capsules. The use of such formats, although practical in a number of such situations, has certain disadvantages associated therewith. For example, the non-medicament components of the tablet or capsule may negatively impact or be incompatible with the medicament itself. Further, the use of tablets or capsules generally precludes absorption of the medicament by the oral cavity of the recipient (the tablet or capsule having to be first be broken down by the recipient's body before the medicament can be absorbed). This required breakdown of the medicament-carrying delivery format thus delays absorption of the medicament for what may be a medically significant period of time. More to the point, certain medicaments and active ingredients are incompatible with the fluids encountered in the digestive system of the recipient. Finally, certain individuals such as the elderly, have difficulty swallowing tablets and/or capsules.
To address several of the disadvantages associated with the use of tablet and/or capsule delivery formats, the prior art has experimented with the use of powdered medicaments which may be delivered directly to the oral cavity of a recipient. These powdered medicaments, which may be manufactured by processes such as spray congealing, spray drying and granulation processing, are typically delivered to the oral cavity of a recipient by other conventional delivery formats, namely mechanized delivery devices, such as low velocity spray apparatuses including various powder blower devices and inhaler devices. The prior art is replete with examples of such devices.
The delivery of powdered medicaments to the oral cavity of a recipient by means of a low velocity spray apparatus is also not without its disadvantages. For example, the fact that the medicament has been produced in powdered form necessitates the need for the use of a delivery instrument. With respect to the blowers and inhalers used to deliver powdered medicament, it is often difficult to ensure that an accurate dosage of such medicament is consistently delivered to the recipient. Moreover, the delivery instrument must be carried at all times by the recipient and maintained in proper working condition. It will be appreciated by those skilled in the art that such instruments are often bulky and/or burdensome to transport and, further, increase the total cost associated with delivery of the medicament to the recipient. Moreover, because the same instrument is used for a plurality of applications of medicament to the recipient, the sterility of the instrument must not be compromised.
The prior art has also experimented with the delivery of medicaments by use, for example, of a propellant-containing dosage inhaler. Such devices normally include a pressure unit that contains the propellant. The active compound may either be dissolved in the propellant or suspended in the propellant in solid micronized form. Again, because of the physical form of the medicament, a mechanized device having the above-discussed limitations is necessary to deliver the substance to the recipient.
Thus, the prior art has attempted to deliver medicaments and other active ingredients directly to a recipient in the absence of delivery formats such as tablets, capsules and mechanized devices and/or instruments such as low velocity spray apparatuses. There is therefore a need in the art for a dosage delivery format which allows direct delivery of the dosage to the recipient.
Over the years considerable time, energy and expense have been expended to devise methods for producing substances having unique morphologies in order to meet different requirements for utilizing a variety of substances. For example, it has been found that multiparticulates are useful in providing bio-availability of active ingredients to a recipient subject. Dosage units prepared from multiparticulates are able to introduce active ingredients in a form which a) disperses freely, b) maximizes absorption by increased surface area, while c) toxicity is minimized.
Within the last two decades, investigation in the area of multiparticulates has resulted in the development of spheroidal particles carrying active ingredients for delivery to a bio-system. This process, in general, will be referred to from time to time herein as spheronization. Spheronization has led to the development of several technologies such as spherical agglomeration (e.g., balling, pelletizing), spray congealing, and cryopelletization.
For example, spherical agglomeration processes employ the uses of inclined dish pelletizers, rotary fluidized bed granulators, and marumerizers. Each of these systems rely primarily on liquid bridging and intermolecular and electrostatic forces for binding, often employing binding agents as a necessary part of the formulation. The dish pelletizing process has been found most useful for production of non-powder agglomerations. In order to produce powder agglomerations, a rotary fluidized bed granulator has been used. This process can produce particles which are smaller than that produced using a dish pelletizer.
In spray congealing processes, the drug or active ingredient can be melted or dispersed in hot melts of waxes, fats, and other materials such as excipients. The molten mass is atomized using air, ultra-sound, or a spinning disk. Usually, this process results in a wide distribution of particle sizes, and care must be taken to obtain the correct range of sizes desired for the particular application. Spray congealing is not considered useful for preparing particulates which include heat sensitive drugs since the exposure to high temperature can be inimical to the stability and viability of the active ingredient.
Indeed, the need for preparing particulates which include heat sensitive active ingredients has led to another recent advancement of spheronization technology which is referred to as cryopellitization. Cryopellitization includes the dissolution or dispersion of a drug or active ingredient with water fillers and binders. The viscosity of the resulting dissolution system is very low. Consequently, the dissolution can be poured into liquid nitrogen and thereby form droplets as the dissolution system falls through the nitrogen. The droplets quickly freeze and are later lyophilized to produce fairly large bead like granules having a largest dimension (e.g., diameter) of 0.8 to 2.0 millimeters. While cryopellitization reduces the disadvantage of heat stress generally related to solvent-free products, disadvantages include cost of production, particle size, and output.
Yet another process, referred to as marumerizing is a method whereby a wet paste prepared from a drug or active ingredient, water and a binder is extruded through a screen to produce extrudate. The extrudate is chopped as it exits the extruder opening to produce rod-shaped particles. The rod-shaped particles are further shaped into spheroids using centrifugal and frictional forces provided by a rotating plate. Marumerizing suffers from several disadvantages including composition requirements, difficult and involved processing steps, and mechanical and electrical energy required to drive the processing equipment. Moreover, it is difficult to maintain a high degree of size and shape consistency by the marumerizing process.
None of the processes presently known in the art of particulate preparation have been able to take advantage (at commercial manufacturing volume) of natures ability to form masses of material with a high degree of consistency.
In commonly-owned copending U.S. patent application Ser. No. 08/269,647 filed Jul. 1, 1994 entitled "Flash Flow Formed Solloid Delivery Systems" (the contents of which are incorporated herein by reference), a method of forming a solloid is disclosed. The solloid formation procedure involves feeding a composition, which includes an active-bearing non-fat substrate and a solid fat at room temperature, preferably to an extruder, subjecting the composition to flash flow conditions, and expelling the composition in a flowable state while applying disruptive force to the composition to form discrete solids. The method includes a carrier element in which an active ingredient is carried.
There is therefore a need in the art for a highly efficient and predictable means of naturally forming minute masses of material on a commercial scale. More to the point, there is a need in the art for a delivery system and/or method of delivering a bio-affecting agent or other active ingredient directly to a recipient in the absence of conventional delivery formats such as tablets, capsules, and mechanized delivery devices or instruments. Other and further objects of the present invention will be realized by those skilled in the art in view of the disclosure set forth herein.